| Objective:To establish the rat model of type 2 diabetes mellitus?T2DM?,observe the expressions of transforming growth factor-?1?TGF-?1?,Smad3,Smad7,type 1 collagen?Col-1?in the thoracic aorta at different time?4,8,12 weeks?;and meanwhile compare the changes of TGF-?1,Smad3,Smad7,Col-1 of thoracic aortic tissue at 4,8,12 weeks after globular adiponectin?gAd?administration between intervention group and model group rats,investigate the association between g Ad and TGF-?1/Smads signaling pathway and mechanism of gAd's protective effects on atherosclerosis?AS?in T2 DM rats,and provide new ideas on the development of prevention and treatment of T2 DM macrovascular complications in clinic.Methods:Ninety male sprague-dawley?SD?rats were randomly divided into normal control group?group N,n=24?and T2 DM model group?n=66?,and similarly fifty-three successfully-induced diabetic rats were divided into T2 DM model group?group D,n=26?and intervention group?group A,n=27?again.Rats in group A were given gAd in dose of 10 ?g·kg-1·d-1,and the other two groups were given equal volume of normal saline.At the end of 4,8 and 12 weeks,selecting eight rats in each group randomly and collecting blood samples for the test of fasting plasma glucose?FPG?,total cholesterol?TC?,triglyceride?TG?,low density lipoprotein cholesterol?LDL-C?,high density lipoprotein cholesterol?HDL-C?after anaesthetized,then preserving the thoracic aortic,observing morphological changes by light microscope after HE staining,using immunohistochemical method to detect the expression of Col-1,and using Western blotting and real time fluorescent quantitative polymerase chain reaction?RT-PCR?method to detect the expressions of TGF-?1,Smad3,Smad7 protein and mRN A.According to the experimental results and statistical analysis,to explore the relationship between them.Results:1.In each time period,the levels of FPG,TC,TG and LDL-C in group D were higher than those in group N significantly,while HDL-C decreased;The levels of FPG,TC,TG and LDL-C in group A were lower than group D of the same period,while HDL-C increased?P<0.05?.2.HE staining showed: in group N,the three layers structure of the inner,middle and outer membrane of the arterial wall of rats were complete,the wall was smooth,and the inner layer and middle layer cells arranged rule.In group D,the boundaries of the inner,middle and outer membrane were unclear,mild disorder,endometrial integrity disrupted,endothelial cells partially disintegrated,mesangial smooth muscle cells varied in shape,number of cells increased and irregular arrangement;and with the duration of T2 DM,the lesions showed a time-dependent increase.After the intervention of gAd,the above lesions of group A were smaller than the corresponding group D,and with the intervention time extending,the degree of AS lesions was time-dependent reduction.3.Immunohistochemical method,Western blotting and RT-PCR showed: the expressions of TGF-?1,Smad3,Col-1 in group D were significantly higher than those in group N,while Smad7 decreased;the expressions of TGF-?1,Smad3,Col-1 in group A were significantly lower than those in group D,while Smad7 increased.And with the intervention time extending,the expressions of TGF-?1,Smad3,Col-1 decreased,Smad7 increased gradually?P<0.05?.Conclusion:1.In the thoracic aorta of T2 DM model group,the expressions of TGF-?1,Smad3 and Col-1 were significantly increased,while the expressions of Smad7 decreased,and with the extension of the course,the levels of TGF-?1,Smad3 and Col-1increased,Smad7 decreased,consisting with the degree of AS lesions of thoracic aortic under light microscope.Suggesting that the abnormal expression of TGF-?1/Smads signaling pathway may be involved in the occurrence and development of AS ratswith T2 DM.2.In the thoracic aorta of gAd intervention group,the expressions of TGF-?1,Smad3 and Col-1 were significantly decreased,while the expression of Smad7 was increased,and with the extension of the course,the levels of TGF-?1,Smad3 and Col-1 decreased,Smad7 increased.The degree of AS lesions of thoracic aortic gradually reduced.It is suggested that gAd can interfere with TGF-?1/Smads conductionpathway by up-regulating Smad7 or down-regulating TGF-?1 and Smad3,and further inhibit the formation and deposition of fibrosis factor such as Col-1,and exert anti-vascular wall fibrotic action,then alleviate the AS process of T2 DM rats. |
PDF Full Text Request